Problems of Radiation Medicine and Radiobiology

E. A. Djomina

R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, 45 Vasylkivska St., 03022, Kyiv, Ukraine

THE DEPENDENCE OF DOSE-EFFECTS IN HUMAN RADIATION CYTOGENETICS

Objective. To study the frequency and spectrum of chromosome aberrations in human peripheral blood lymphocytes depending on the radiation dose, the stage of the mitotic cycle and the periods of fixation of the cell culture.
Materials and methods. The test system of blood lymphocytes of donors, the metaphase analysis of chromosome aberrations (a uniform staining of the drugs). The gamma-irradiation was performed on the device with the source ⁶⁰Co at the dose rate of 0.5 Gy/min, the dose range was 0.25–4.0 Gy. The lymphocyte culture was irradiated after 0, 24, 40 and 48 hours from the beginning of the incubation, which corresponds to G₀-, G₁-, S-, G₂-stages of the mitotic cycle. The cells were fixed after 52 hours and 62 hours from the beginning of the incubation.
Results. The author’s experimental data on the regularities of chromosome aberrations formation during irradiation at the different periods of the mitotic cycle of human lymphocyte culture are presented. The character of the dose dependences of structural damages of chromosomes during the mitotic cycle with an application of the linear, linear-square and parabolic models is analyzed. The greatest yield of exchange-type aberrations is registered at the irradiation in G₀- and G₁-stages of the mitotic cycle, which submits to the linear-square dependence on an irradiation dose. When irradiating cells in the S- and G₂-stages, the main contribution to the spectrum of radiation-induced chromosome aberrations is made by deletions, the level of which increases linearly with the dose. This is evidenced by the negative values of the quadratic term in the regression equations for these stages. The analysis of the curves using the parabolic model Y = k · Dn has shown that, at the irradiation of lymphocytes in G₀- and G₁-stages, the dose dependences approach the quadratic ones, which confirms the reasonableness of the interpretation of the obtained cytogenetic data from the point of view of the «classical» theory of the radiation-induced chromosome aberrations formation. However, the model of the spline regression is more accurate at the approximation of the dependences of the cytogenetic effects in the region of low doses of irradiation.
Conclusions. The results obtained by the irradiation of human lymphocyte culture at different stages of the mitotic cycle indicate that the same radiation dose induces different qualitative and quantitative cytogenetic effects depending on the physiological state of the cell at the time of irradiation. The combination of such factors as a radiation dose rate, a mitotic cycle stage, the post-irradiation conditions, and an individual radiosensitivity are reflected in quantitative and qualitative variations of the cellular radiosensitivity.
Key words: lymphocytes, chromosome aberrations, irradiation, mitotic cycle, dose dependencies, mathematical models.

Problems of Radiation Medicine and Radiobiology.
2019;24:235-249. doi: 10.33145/2304-8336-2019-24-235-249

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